Sex-dependent features of social behavior differ between distinct laboratory mouse strains and their mixed offspring

Kopachev, Natalia; Netser, Shai; Wagner, Shlomo

doi:10.1016/j.isci.2022.103735

Cited by 14 publications

(15 citation statements)

References 36 publications

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“…In line with our findings, human data indicates that male, but not female, Met66BDNF allele-carriers experience higher incidences of major depressive disorder [56]. In addition, sex differences in social behavior have been widely described [57][58][59][60][61][62], and are likely to be caused by differences in neuronal activity, receptor density and hormonal signaling. However, further studies are needed to determine whether BDNF in female mice plays a role in other behaviors, including gating alcohol use [63], which is mediated in part via corticostriatal circuitries [31].…”

Section: Discussionsupporting

confidence: 89%

“…Sex differences in social behavior have been widely described [54][55][56][57][58][59]. Interestingly, we observed sex differences in social behaviors between the male and female Met68BDNF mice.…”

Section: Discussionsupporting

confidence: 50%

“…Sex differences in social behavior have been widely described [54–59], and we observed sex differences in social behaviors between the male and female Met68BDNF mice. Specifically, disruption in BDNF function does not seem to affect the social behavior phenotypes in female Met68BDNF, and in contrast male Met68BDNF mice exhibit social anxiety.…”

Section: Discussionmentioning

confidence: 58%

“…In addition, sex differences in social behavior have been widely described [50][51][52][53][54][55]. However, further studies are needed to determine whether BDNF in female mice plays a role in other behaviors, including gating alcohol use, which is mediated in part via corticostriatal circuitries in male mice [14,[56][57][58].…”

Section: Discussionmentioning

confidence: 99%

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The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice

Moffat

Sakhai

Hoisington

et al. 2022

Preprint

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The brain-derived neurotrophic factor (BDNF) Valine 66 to Methionine human polymorphism results in impaired activity-dependent BDNF release and has been linked to psychiatric disorders including anxiety and alcohol dependence. We previously showed that knock-in mice carrying the mouse Methionine homolog (Met68BDNF) exhibit excessive and compulsive alcohol drinking behaviors as compared to the wild-type Val68BDNF mice. Here, we set out to determine the potential mechanism for the heightened and compulsive alcohol drinking phenotype exhibited by the Met68BDNFmice. We found that male, but not female Met68BDNF mice show social anxiety-like behaviors. We further report that male, but not female, Met68BDNF mice are resistant to the anxiolytic effects and sedative actions of alcohol as compared to Val68BDNF mice. Alcohol-dependent hypolocomotion is also reduced in Met68BDNF. In contrast, alcohol place preference is similar in Met68BDNF compared with Val68BDNF mice. Finally, we show that the anxiolytic action of alcohol is restored in Met68BDNF mice by overexpressing the wild-type Val68BDNF in the ventral hippocampus (vHC). Together, our results suggest that heighted social anxiety and a lack of alcohol-dependent anxiolysis may contribute to excessive alcohol intake by constraining normal BDNF signaling in the vHC.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice

Moffat

Sakhai

Hoisington

et al. 2022

Preprint

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“…Male and female KO, WT, and pure WT mice performed multiple social discrimination tasks, as previously described 14,50,51 . Each session comprised 15 minute window of habituation in the arena with empty triangular chambers in opposing corners of the arena, as previously described 52 , followed by the subject mice performing the task of interest for 5 minutes (encounter).…”

Section: Methodsmentioning

confidence: 99%

Impaired emotion recognition inCntnap2-deficient mice is associated with hyper-synchronous prefrontal cortex neuronal activity

Mohapatra,

Jabarin,

Ray

et al. 2023

Preprint

Self Cite

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Individuals diagnosed with autism spectrum disorder (ASD) show difficulty in recognizing emotions in others, a process termed emotion recognition. While human fMRI studies linked multiple brain areas to emotion recognition, the specific mechanisms underlying impaired emotion recognition in ASD are not clear, partially due to the lack of appropriate tests in animal models. Here, we employed an emotional state preference (ESP) task to show that, unlike C57BL/6J mice, Cntnap2-knockout (KO) mice, an established ASD model, do not distinguish between conspecifics according to their emotional state. We assessed brain-wide local-field potential (LFP) signals during various social behavior tasks and found that Cntnap2-KO mice exhibited higher LFP theta and gamma rhythmicity than did C57BL/6J mice, even at rest. Specifically, Cntnap2-KO mice showed increased theta coherence, especially between the prelimbic cortex (PrL) and the hypothalamic paraventricular nucleus, during social behavior. Moreover, we observed significantly increased Granger causality of theta rhythmicity between these two brain areas, across all types of social behavior. Finally, optogenetic stimulation of PrL pyramidal neurons in C57BL/6J mice impaired their social discrimination abilities, including ESP behavior. Together, these results suggest that increased activity of PrL pyramidal neurons and their augmented synchronization with specific brain regions are involved in the impaired emotion recognition exhibited by Cntnap2-KO mice.

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The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice

et al. 2023

View full text Add to dashboard Cite

Background The brain-derived neurotrophic factor (BDNF) Valine 66 to Methionine human polymorphism results in impaired activity-dependent BDNF release and has been linked to psychiatric disorders including depression and anxiety. We previously showed that male knock-in mice carrying the mouse Methionine homolog (Met68BDNF) exhibit excessive and compulsive alcohol drinking behaviors as compared to the wild-type Val68BDNF mice. Objective Here, we set out to determine the potential mechanism for the heightened and compulsive alcohol drinking phenotypes detected in Met68BDNF mice. Results We found that male, but not female Met68BDNF mice exhibit social anxiety-like behaviors. We further show that male Met68BDNF mice exhibit a preference for alcohol over social interaction. In contrast, alcohol place preference without an alternative social reward, is similar in male Met68BDNF and Val68BDNF mice. Since the Met68BDNF mice show social anxiety phenotypes, we tested whether alcohol reliefs anxiety similarly in Met68BDNF and Val68BDNF mice and found that male, but not female Met68BDNF mice are insensitive to the acute anxiolytic action of alcohol. Finally, we show that this acute tolerance to alcohol-dependent anxiolysis can be restored by overexpressing wild-type Val68BDNF in the ventral hippocampus (vHC) of Met68BDNF mice. Conclusions Together, our results suggest that excessive alcohol drinking in the Met68BDNF may be attributed, in part, to heighted social anxiety and a lack of alcohol-dependent anxiolysis, a phenotype that is associated with malfunction of BDNF signaling in the vHC of male Met68BDNF mice.

show abstract

Sex-dependent features of social behavior differ between distinct laboratory mouse strains and their mixed offspring

Cited by 14 publications

References 36 publications

The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice

The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice

Impaired emotion recognition inCntnap2-deficient mice is associated with hyper-synchronous prefrontal cortex neuronal activity

The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice

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